A CLINICOPATHOLOGICAL AND BRAIN MRI STUDY IN EGYPTIAN CHILDREN WITH MITOCHONDRIAL DISORDERS

Objectives: This prospective study was undertaken to focus on the clinicopathological aspects as well as the value of brain MRI in children suffering from mitochondriopathies.

Methods: 31 patients (15 males (48.4%) and 16 females (51.6%) gathered from the neuropediatric and metabolic clinic of Cairo University Children Hospital were included in this study. All patients were subjected to a thorough history and a meticulous clinical examination, CT& or MRI, EMG &NCV. Muscle biopsies were performed in 18/31 patients and were subjected to both COX staining and electron microscopic examination. Laboratory tests including serum lactate and pyruvate, CPK, urine and plasma aminogram, urine organic acid profile, acyl carnitine profile, enzymatic analysis for arylsulfatase, galactocerebrosidase, VLCFA, acetyl aspartase were also performed when needed.

Results: Patients were classified according to their clinical phenotypes into: mitochondrial leukoencephalopathy (3/31), leigh syndrom (7/31), NARP (2/31), mitochondrial encephalomyopathy (6/31), LHON 4/31), MERRF (1). MELAS (1), familial dystonia (4/31), and mitochondrial myopathy (3/31). The main neurological manifestations in their order of frequency were: global developmental delay (20, 64.5%), spasticity (16, 51.6%), hypotonia (12, 38.7%) convulsions, (10, 32.3%), sensory neural deafness (7, 22.6%), dystonia (7, 22.6%) optic atrophy (5, 16.1%), proximal muscle weakness (3, 9.7%), retinitis pigmentosa (2, 6.5%) & ataxia (2, 6.5%), EMG and nerve conduction study were normal in 18/31(58%), myopathic in 7/31(22.6% and neuropathic in 6/31(19.4%) patients. CPK was significantly increased in only 3/31(9.7%) patients. The main MRI findings were basal ganglia abnormalities appearing as bilateral & symmetrical high signal intensity lesions on T2W MRI (11/28, 39.3%). MRS was performed in 7 patients and all were showing an increase lactate peak. Electron microscopic examination revealed a subsarcolemmal aggregation of mitochondria in (12/18, 66.7%)& or a large and bizarre shaped mitochondria in (8/18, 44.4%), non specific myopathic changes in (3/18, 16.7%). Histochemical analysis of muscle biopsies using cytochrome oxidase staining revealed a COX -ve in (5/11, 45.5%), COX +ve in (6/11, 54.5%), and myopathic changes in (3/18, 16.7%) patients.

Conclusion: MRI and MRS proved to be a promising tool in the diagnosis of mitochondriopathies by demonstration of high lactate peak in the brain of these patients even in the absence of an increased blood or CSF lactate. Muscle biopsy examined by both histochemistry and electron microscopy is considered the most valuable diagnostic tool. Nevertheless, there are few patients in whom the diagnosis would remain to be confirmed by biochemical and molecular studies.